Glaucoma refers to a group of eye conditions that lead to damage to the optic nerve (the nerve that carries visual information from the eye to the brain). In many cases, damage to the optic nerve is due to increased pressure in the eye, also known as intraocular pressure (IOP). Glaucoma is the second most common cause of blindness in the United States. There are three major types of glaucoma: open-angle glaucoma or chronic glaucoma, congenital glaucoma, and angle closure (acute) glaucoma.
The front part of the eye is filled with a clear fluid called aqueous humor that is produced by the ciliary body, which forms a barrier between the anterior and posterior chambers of the eye. This fluid leaves the eye through channels in the front of the eye in an area called the anterior chamber angle, or simply the angle. Anything that slows or blocks the flow of this fluid out of the eye will cause pressure to build up in the eye. This pressure is called intraocular pressure (TOP). In most cases of glaucoma, this pressure is high and causes damage to the optic nerve, the major nerve in the eye.
Open-angle (chronic) glaucoma is the most common type of glaucoma, but its cause is unknown. An increase in eye pressure occurs slowly over time. The pressure pushes on the optic nerve and the retina at the back of the eye. Open-angle glaucoma tends to run in families. The risk is higher if a patient has a parent or grandparent with open-angle glaucoma, and people of African descent are at particularly high risk for this disease. Most people have no symptoms until they begin to lose vision and then experience gradual loss of peripheral (side) vision (also called tunnel vision).
Angle-closure (acute) glaucoma occurs when the exit of the aqueous humor fluid is suddenly blocked. This causes a quick, severe, and painful rise in the pressure within the eye (intraocular pressure). Angle-closure glaucoma is an emergency. This is very different from open-angle glaucoma, which painlessly and slowly damages vision. Symptoms of angle-closure glaucoma may come and go at first, or steadily become worse and may develop into sudden, severe pain in one eye, decreased or cloudy vision, nausea and vomiting, rainbow-like halos around lights, red eye, and a swollen sensation in the eye.
Congenital glaucoma often is hereditary and results from the abnormal development of the fluid outflow channels in the eye. The symptoms are usually noticed when the child is a few months old and they include cloudiness of the front of the eye, enlargement of one eye or both eyes, red eye, sensitivity to light, and tearing.
An eye exam may be used to diagnose glaucoma. The physician will need to examine the inside of the eye by looking through the pupil, often while the pupil is dilated. The physician will usually perform a complete eye exam. Checking the intraocular pressure alone (tonometry) is not enough to diagnose glaucoma because eye pressure changes. Pressure in the eye is normal in about 25% of people with glaucoma. This is called normal-tension glaucoma. There are also other problems that cause optic nerve damage, thus necessitating a complete eye exam.
Tests to diagnose glaucoma include: gonioscopy (use of a special lens to see the outflow channels of the angle), tonometry test to measure eye pressure, optic nerve imaging (photographs of the inside of the eye), pupillary reflex response, retinal examination, slit lamp examination, visual acuity, and visual field measurement.
Although some forms of glaucoma treatment are available, none are adequate. Thus, there remains a need for a therapeutic regimen that is easy to administer, has minimal or no side effects, and that has long lasting efficacy. The goal of current treatment is to reduce eye pressure. Depending on the type of glaucoma, this is currently done using medications or surgery. Most people with open-angle glaucoma can be treated with some degree of success with these pressure lowering eye drops. However, most eye drops used today continue to have unpredictable side effects. Many times, more than one type of drop may be necessary. Some patients may also be treated with pills to lower pressure in the eye. Improved eye drops and pills that may protect the optic nerve from glaucoma damage are desirable. Some patients need other forms of treatment, such as laser treatment, to help open the fluid outflow channels. This procedure is usually painless. Others may need traditional surgery to open a new outflow channel.
Angle-closure glaucoma treatment requires immediate medical intervention. Acute angle-closure attack is a medical emergency and blindness will occur in as little as a few days if the closure is not treated. Drops, pills, and medicine given through a vein (by IV) are used to lower pressure. Some people also need an emergency operation, called an iridotomy. This procedure uses a laser to open a new channel in the iris. The new channel relieves pressure and prevents another attack. But, this procedure is not without the risk of side effects, which include a transient increased TOP, inflammation within the eye, damage to the corneal epithelium, opacification of the cornea, bleeding of the iris, and macular edema. Some patients also experience glare and double vision after the procedure, and there may also be a transient blurry vision.
As for congenital glaucoma, treatment almost always requires surgery to open the outflow channels of the angle. This is done while the patient is under anesthesia so that the patient feels no pain during the procedure. But like any surgery, side affects such as post-operative pain and infection may occur.
An alternative strategy is to block cell death by a gene independent approach, such as treatment with neuroprotective therapy. Gene delivery of erythropoietin (EPO) overcomes two major challenges associated with neuroprotective therapy. First, virus mediated gene delivery provides long term gene expression, overcoming the need for repeat delivery because of the short half-life of most neuroprotective agents. Second, EPO, unlike other neuroprotective proteins, is able to cross the blood retina and blood brain barrier. One major problem associated with the administration of EPO, however, is a rise in hematocrit levels.
What are needed are improved and effective compositions and methods for the treatment of disorders associated with retinal degeneration, such as glaucoma, that are independent of intraocular pressure. More specifically, what are needed are compositions and methods for systemic delivery of therapeutic agents having quick and long lasting effects and minimal side effects.